This proposed research concerns the identification and study of hereditary metabolic disorders of amino acids, organic acids and related compounds in the human, particularly those causing mental retardation and other neurological and metabolic abnormalities. In addition, infants diagnosed as having metabolic disorders on the basis of biochemical abnormalities detected by newborn screening will be investigated and treated, if necessary. New therapeutic regimens and laboratory techniques for the detection of metabolic disorders will be developed. Fibroblast culture techniques will be utilized in most instances for enzyme diagnosis and for studying the nature of enzyme defects. The disorders to be studied include abnormalities in sulfur amino acid metabolism, ornithine metabolic errors, urea cycle disorders, galactosemia, methylmalonic acidemia, and other rare organic acidemias. We wil also study normal amino acid metabolism as well as the effect of metabolic defects in animals.